Indocyanine green fluorescence imaging in gastric cancer: Clinical efficacy, technical innovations, and future perspectives

Abstract

Gastric cancer (GC) ranks among the most common and deadly malignancies globally. Surgical resection with lymph node (LN) dissection is the primary treatment. The accuracy of LN dissection is essential to reduce postoperative complications and mortality. Therefore, improving the quality of LN dissection in GC surgery and refining postoperative LN staging have been the focus of clinical attention. Indocyanine green (ICG) fluorescence imaging serves as a vital clinical tracing technique in GC surgery. It enables accurate tumor localization, enhances the completeness of LN dissection, and evaluates anastomotic blood supply after digestive tract reconstruction. These benefits collectively improve surgical outcomes and lower recurrence rates. This article examines the principles of ICG fluorescence imaging and its necessity in GC tracing surgery. Compared to conventional tracers, ICG offers superior safety and lower toxicity, with robust evidence supporting its clinical efficacy. This technology represents a paradigm shift in GC surgery. Current studies optimize ICG delivery protocols, such as injection time and dose, and integrate it with emerging technologies like robotic systems to improve LN detection rates. This article demonstrates the safety and efficacy of ICG as a tracer, which is poised to advance the precision of GC surgery and improve patient outcomes.

Key Words: Indocyanine green; Fluorescence imaging; Gastric cancer; Lymph node dissection; Near-infrared imaging

Core Tip: The accuracy of lymph node dissection is crucial for reducing postoperative complications and mortality in gastric cancer (GC). Indocyanine green fluorescence staining, as a clinical tracer technique, plays an important role in GC surgery. It enables accurate tumor localization, enhances the thoroughness of lymph node dissection, and facilitates assessment of anastomotic blood supply following digestive tract reconstruction. These functions contribute to improved surgical outcomes and reduced recurrence rates. This review highlights the safety and efficacy of indocyanine green as a tracer, which is expected to enhance surgical precision and improve patient prognosis in GC.

INTRODUCTION

Gastric cancer (GC) is the fifth most prevalent form of cancer worldwide, with an annual incidence of over 1 million cases, and the fourth leading cause of cancer death, accounting for 7.7% of all malignancy deaths[1]. GC is characterized by a high tendency for lymph node (LN) metastasis, and radical surgery is the most effective treatment for GC. However, 87.5% of patients with local recurrence after radical resection exhibit LN metastasis[2]. Increased lymphangiogenesis and LN metastasis are important steps in GC metastasis and are associated with poor patient prognoses[3]. Achieving complete tumor resection with adequate margins is essential in gastrectomy. Securing sufficient proximal surgical margins enhances cure rates while minimizing recurrence risks.

Adequate lymphadenectomy and securing sufficient surgical margins represent critical components for the success of curative surgery in GC[4]. The number of LN detected is closely related to pathological stage and prognosis[5]. According to the 6^th Edition of the Japanese Guidelines for the Treatment of GC (2021), D2 LN dissection should detect a minimum of 12 LNs for total gastrectomy, 11 for distal gastrectomy, and 10 for proximal gastrectomy[6]. The National Comprehensive Cancer Network guidelines recommend that resection margins be ≥ 4 cm[7]. According to the guidelines of the Japan Gastric Cancer Association, the resection margin of patients with early GC and advanced GC should be at least 3 cm and 5 cm, respectively, and marginal resection following the guidelines can improve the survival outcomes of patients[8].

The application of laparoscopic radical surgery to patients with GC has been gradually increasing, and recent studies have demonstrated its safety and feasibility. However, the inability of laparoscopic surgery to locate tumors and LNs through palpation poses a significant challenge in distinguishing tumor sites and identifying resection lines[9]. Indocyanine green (ICG) has been introduced into laparoscopic gastrectomy due to its ability to enhance visualization during surgery, which is particularly advantageous for sentinel LN (SLN) mapping and LN dissection[10]. In addition, there is a risk of potential metastasis of LNs in fat tissue, and these nodes are difficult to detect during surgery. Compared to other tracers, ICG fluorescence demonstrates greater tissue penetration during laparoscopic imaging, enabling more precise identification of tumors and LNs within thickened adipose tissue[11].

PRINCIPLE AND APPLICATION OF ICG

ICG is a hydrophilic, tri-carbocyanine fluorescent dye and has been approved by the United States Food and Drug Administration and the European Medicines Agency[12]. ICG has a half-life of 2 minutes to 4 minutes, with hepatic metabolism and excretion via the bile ducts, typically occurring within 15 minutes to 20 minutes, and there is no evidence of renal toxicity[13]. As a near-infrared (NIR) fluorophore, ICG is excited at wavelengths of 750-810 nm and emits fluorescence at wavelengths of 830-840 nm, which can be detected by a NIR camera (Figure 1)[14]. The NIR light emitted by ICG is an optical reaction that does not involve radiation. The favorable characteristics of NIR light, including its low absorption, low scattering, and low auto-fluorescence, enable greater tissue penetration compared to visible light.

Figure 1 The value of indocyanine green fluorescence imaging in gastric cancer surgery. ICG: Indocyanine green.

When bound to plasma proteins, ICG exhibits a shift in its maximum absorption wavelength to 805 nm[15]. When exposed to light approaching the maximum absorption wavelength, ICG-injected tissues absorb incident light and emit NIR fluorescence, whereas surrounding tissues reflect illumination and become brighter, enhancing visual contrast. This is the mechanism of infrared light absorption observations using ICG. Upon excitation by NIR light, ICG emits fluorescence at a wavelength of approximately 820 nm, allowing the clear visualization of specific structures such as lymphatic vessels, LNs, and blood vessels[16]. Furthermore, LNs stained with ICG can be clearly visualized under NIR imaging and can be detected to a depth of 3-5 mm[17].

ICG is an excellent choice for imaging due to its hypo-sensitivity, deep detection depth, and high sensitivity in stable signals[18]. ICG is being widely adopted across surgical specialties due to its ability to deliver high-contrast imaging that offers exceptional tissue discrimination and sensitivity. In GC surgery, ICG fluorescence imaging can be used for SLN biopsy and analysis, LN excision guidance and quality control, and tumor localization[19]. The maximum tolerated dose of ICG is 5 mg/kg, while the recommended clinical dose ranges from 0.2 mg/k to 0.5 mg/kg[20]. However, there is still no uniform standard for the dosage of ICG. Subgroup analysis of ICG concentration revealed that the 0.5 mg/mL ICG concentration group was more sensitive in NIR imaging than the 5 mg/mL ICG group[21]. Typically, ICG can be detected within seconds after injection, but the time for fluorescence vary significantly with administration route, anatomic injection site, administered dose[22]. Therefore, the method of ICG use needs to be further standardized.

The injection of ICG can be performed in two ways: Either preoperative submucosal injection surrounding the tumor, or intraoperative subserosal injection (Table 1)[23]. Chen et al[24] found that there were no significant differences in the total number of dissected LNs, the rate and incidence of LN noncompliance between the submucosal group and the subserosal group, and there was no significant difference in the incidence and severity of postoperative complications between the submucosal group and the subserosal group. However, subserosal injection often induces ICG extravasation and surgical field fluorescence diffusion, complicating targeted dissection due to widespread background signal[25]. Compared with intraoperative subserosal injection, preoperative endoscopically guided submucosal injection of ICG is easier to administer, save time, and prevent ICG leakage into the surgical area or enter the blood vessels to interfere with the surgery[26]. Thus, in GC, subserosal injection and submucosal injection of ICG yield similar results in LN tracking, but submucosal injection is undoubtedly a better choice for surgery. There are no discernible contraindications to the use of ICG. However, ICG contains a minimal amount of iodine, so ICG fluorescence imaging is not recommended for patients with iodine allergy.

Table 1 Indocyanine green injection methods comparison in gastric cancer surgery.

Feature	Submucosal injection	Sub-serosal injection
Injection method	Under the guidance of preoperative endoscopy	Intraoperative direct injection
Ease of use	Performed by endoscopist	Performed by surgeon during surgery
	Not occupy surgical time	May be limited by visual field and operational space
Imaging clarity	Fluorescence is concentrated with clear boundaries; beneficial for precise tumor and lymph node localization	Prone to ICG leakage and diffusion; lead to dispersed fluorescence, contaminated surgical field, and significant background interference
Risk of leakage	Low; unlikely to contaminate the abdominal cavity and surgical field	High; prone to leakage into the abdominal cavity, widely contaminating adipose tissue, intestines, and other tissues, severely affecting observation
Impact on surgery	Minimal impact; surgery can proceed as planned even if injection fails or fluorescence is poor	Potential impact; leaked ICG may contaminate the surgical field and interfere with subsequent non-fluorescence guided procedures
Applicability and recommendation	Preferred method; especially suitable for tumor localization and lymph node tracing in early gastric cancer	Applicable when preoperative endoscopy is not feasible
Key advantage	Clean surgical field, high-quality imaging, does not interfere with surgery	No additional preoperative endoscopic procedure required

ICG: Indocyanine green.

APPLICATION OF ICG FLUORESCENCE IMAGING IN GC

LN tracing and dissection

The SLN of the stomach is the primary site of lymphatic drainage in GC, and there is the potential for micro-metastasis and skip metastasis in the complex lymphatic drainage of GC[27]. Tani et al[28] demonstrated that SLN mapping with SLN basin dissection is preferable for early GC since it is minimally invasive. In addition, Tajima et al[29] reported that ICG was effective for SLN identification in both laparoscopically assisted gastrectomy and open gastrectomy. The accuracy and false negative rates of patients in the laparoscopically assisted gastrectomy group were 97.2% and 25.0%, and the accuracy and false negative rates of patients in the open gastrectomy group were 91.9% and 23.1%, respectively. Clinical evidence confirms ICG high efficacy in identifying gastric SLNs. Real-time, in vivo imaging with ICG fluorescence guidance during radical gastrectomy for GC allows for dynamic assessment of regional gastric nodal anatomy and precise topographic localization.

Kim et al[30] demonstrated that ICG fluorescence imaging significantly increases the LN detection rate in laparoscopic surgery. Similarly, Kwon et al[31] demonstrated that no complications related to ICG injection were observed after ICG-guided surgery, and that the mean number of total LNs retrieved was greater in the NIR group than in historical controls, with the number of retrieved LNs significantly higher at stations 2, 6, 7, 8, and 9. Furthermore, all metastatic LNs detected in the 5 NIR-positive patients exhibited fluorescence. Liu et al[10] found that ICG fluorescent labeling significantly increased the number of LNs detected in stations 8-12 during radical gastrectomy. In a prospective randomized controlled study, Chen et al[32] documented significantly higher mean LN yield in ICG-assisted resections vs non-ICG controls during D2 Lymphadenectomy, consistent across both distal and total gastrectomy approaches.

LN non-compliance is an effective evaluation index for assessing the quality of LN resection and is related to the prognosis of patients with GC. With the assistance of ICG, the mean number of LNs retrieved in the ICG group was significantly higher than that in the non-ICG group (49.9 vs 42.0, P < 0.001). When analyzed by pathological tumor (pT) category, a higher proportion of pathological node positive + disease was observed in the ICG group compared to the non-ICG group: PT1 (18.8% vs 15.4%), pT2 (55.9% vs 42.9%), pT3 (78.3% vs 73.7%), and pT4a (91.3% vs 88.5%). Concurrently, the rate of LN noncompliance was significantly lower than that in the non-ICG group (31.9% vs 57.4%, P < 0.001)[33]. The study also concluded that the sensitivity of fluorescence imaging in detecting all metastatic LN stations was 86.8%, while the negative predictive value of non-fluorescence stations was 92.2%. Most significantly, diagnostic accuracy was achieved 100% for clinical tumor stage 1-2 disease metastases within D1+ and D2 Lymphadenectomy fields across all gastrectomy type. Even in the presence of scarring after endoscopic submucosal dissection, ICG fluorescence maintains diagnostic efficacy[34]. In conclusion, ICG-NIR fluorescence imaging can be used by surgeons to dissect more LNs within the same operating field with a similar operative time. This approach leads to a more precise postoperative staging, thus enhancing the accuracy of post-surgical management.

Tumor localization

In the context of surgical intervention for GC, the achievement of negative tumor margins is a critical determinant of overall survival and long-term patient outcomes[35]. Meanwhile, studies have highlighted the necessity to minimize the surgical margin distance while ensuring the safe margin distance to preserve normal tissue in radical surgery for GC. The preservation of a greater quantity of normal stomach tissue has been demonstrated to result in a substantial enhancement in the postoperative quality of life of patients[36]. Therefore, the selection of reasonable and safe resection margin positions is imperative for the prognosis and quality of life of patients. ICG fluorescence imaging facilitates intraoperative tumor localization and precise margin demarcation during gastrointestinal resection procedures. Ushimaru et al[37] found that in GC surgery, preoperative low-dose ICG injection into the peritumoral submucosa enables clear intraoperative visualization of the tumor. Cho et al[38] found that NIR-guided ICG diffusion zones along the gastric wall ensured resection margins of 28 mm or greater. It is evident that ICG has potential value in guiding the accuracy of surgery and improving the postoperative survival and quality of life of patients.

Another critical advantage of ICG fluorescence imaging is that it does not contaminate the surgical area, even if preoperative labeling fails. Additionally, the white light mode of fluorescence laparoscopy can still provide routine surgical visualization, thereby increasing the margin for error in surgery. Although ICG is more easily visualized under fluorescence, it is not visible under natural light. Therefore, any injection error of ICG has no effect on surgical operations conducted without fluorescence guidance. Even in circumstances where ICG staining is either incomplete or excessive, conventional laparoscopic radical resection of GC can be conducted without compromising the surgical outcome[39].

Blood flow assessment

Intraoperative ICG angiography provides real-time visualization of gastric tube vasculature, enhancing perfusion assessment and reducing iatrogenic injury risks. Mina Kim et al[40] injected approximately 3 mL of ICG (2.5 mg/mL) intravenously into 20 patients undergoing robotic or laparoscopic gastrectomy and imaged them with a NIR imaging system. The results demonstrated that the use of ICG facilitated visualization of blood vessels and blood flow during the reconstruction process, thereby enabling the identification of the morphology and origin of small vessels, such as the inferior pyloric artery and accessory splenic artery. This capability can assist surgeons in making better decisions to prevent vascular injury.

A meta-analysis evaluated ICG fluorescence angiography (ICG-FA) efficacy in reducing anastomotic leak (AL) incidence following esophageal cancer resection. The result of this analysis showed that ICG-FA could dynamically assess gastric catheter perfusion and guide the selection of anastomotic site. Furthermore, intraoperative intervention with ICG reduced the incidence of AL by 69%[41]. Mori et al[42] demonstrated in 100 GC patients that the interval between ICG fluorescence appearance across the anastomosis, as assessed by ICG-FA, was an independent predictor of AL. Zhao et al[43] also established ICG fluorescence as an effective perfusion assessment tool for gastric conduits, demonstrating its dual role in enhancing anastomotic microcirculation and lowering AL incidence.

Nerve protection

Radical surgery for GC frequently necessitates the resection of the perigastric vagus nerve, which can result in functional and physiological disorders. Compared with patients undergoing distal gastrectomy with vagus nerve resection, those who undergo laparoscopic distal gastrectomy with neurophysiological monitoring and ICG labeling to preserve the vagus nerve, especially in early GC cases, can maintain the function of the residual stomach and improve postoperative quality of life[44]. This approach is not only safe and feasible but also effective in preserving vagus nerve function. Given the numerous anatomical variations of the vagus nerve, the rational use of ICG labeling can effectively avoid nerve injury, preserve autonomic nerve function, and enhance patient quality of life.

ICG FLUORESCENCE IMAGING IN GC AFTER TRACER SURGERY

Improve patient outcomes

Compared with traditional LN dissection, ICG NIR-guided laparoscopic LN dissection has been demonstrated to reduce postoperative metastasis and recurrence while safely and effectively prolonging the survival of patients with resectable GC. Univariable Cox regression analysis have shown that patients who underwent ICG-guided localization during surgery exhibited significantly superior overall survival [hazard ratio (HR) = 0.53, 95% confidence interval (CI): 0.29-0.96] and disease-free survival (HR = 0.53, 95%CI: 0.32-0.88) than those who did not undergo ICG-guided localization[45]. The study also found that the overall recurrence rate in the ICG group was 17.8%, much lower than the 31.0% in the non-ICG group (HR = 0.54; 95%CI: 0.32-0.91; adjusted P = 0.020). Furthermore, Niu et al[46] further demonstrated that ICG NIR-guided radical gastrectomy significantly lowers postoperative morbidity, especially those of Clavien-Dindo Grade II and above. The use of ICG-FA provides surgeons with detailed visualization of tissue perfusion, facilitating the assessment of gastric blood perfusion during surgery. Furthermore, ICG-guided perfusion analysis of GC has been shown to assist surgeons in the construction of the anastomosis, the avoidance of intraoperative vascular injury, the reduction of intraoperative blood loss, and potentially decrease incidence of AL[41]. Preserving the vagus nerve through neurophysiological monitoring and ICG labeling can reduce the incidence of postoperative gastroparesis and gallstones, as well as significantly lower the incidence of postoperative anorexia, reflux symptoms, and eating difficulties, thereby improving patients' postoperative quality of life[44].

Reduce operation time

A study of 1332 GC patients after laparoscopic gastrectomy linked prolonged operative duration to elevated postoperative complication risks[47]. In GC surgery, ICG simultaneously improves tumor targeting accuracy and shortens surgical time. A retrospective comparative study including 93 GC patients showed that the median operative time was 235 minutes in the ICG group and 275 minutes in the non-ICG group[48]. Similarly, Ushimaru et al[37] divided patients into ICG (n = 84) and non-ICG (n = 174) groups based on whether they received preoperative endoscopic submucosal ICG injection and found that the ICG group exhibited a significantly reduced operation time for laparoscopic GC surgery (206.1 ± 5.0 minutes vs 237.0 ± 5.0 minutes, P < 0.001). Beyond reducing operative duration vs conventional methods, ICG may lower postoperative complication rates, enhancing its clinical value.

IMPROVEMENT OF ICG FLUORESCENCE IMAGING TECHNOLOGY

Technical limitation

While ICG enhances LN detection sensitivity, it lacks specificity for metastatic identification. High false-negative results during intraoperative histopathology significantly limit SLN biopsy clinical utility in early-stage GC[49]. Metastatic LN counts showed no significant difference between ICG and non-ICG cohorts, regardless of whether conventional or laparoscopic gastrectomy was performed. ICG fluorescence demonstrated 56.3% sensitivity and 46.1% specificity for metastatic LN detection[32]. This may be due to cancer cells blocking lymphatic vessels or massive cancerous infiltration of LNs, preventing the administered tracer from accumulating in positive LNs[50]. With advancing clinical adoption and innovation in ICG systems, this modality diagnostic precision is anticipated to increase.

Currently, there is no standardized or uniform quantitative method for measuring the fluorescence intensity of ICG, which means that surgeons must rely on their subjective visual judgment. Previous studies have explored this issue. By comparing the fluorescence intensity of each LN with surrounding background, Takahashi et al[17] categorized 563 LNs into ICG-positive and ICG-negative groups under infrared light observation. Among 563 LNs analyzed, ICG-positive specimens (n = 358) exhibited significantly lower fluorescence intensity ratios vs ICG-negative specimens (n = 205) demonstrating a marked intergroup difference (P < 0.0001). This study explored the potential for establishing quantitative ICG fluorescence standards. However, the method employed by the aforementioned team involved time-consuming ex vivo examinations, which are not feasible for practical clinical application. Similarly, Kim et al[51] identified SLNs by quantitatively estimating ICG fluorescence signal intensity and suggested that an appropriate threshold for SLN detection should be set at 10% of the maximum signal intensity. Although these studies provide an initial exploration of quantitative ICG, they are limited by factors such as small sample sizes, tumor heterogeneity, the inherent properties of ICG, or other issues. However, Boland et al[52] found that artificial intelligence could be used to quantify and classify fluorescent perfusion signals in real time to better assist ICG perfusion imaging. Therefore, integrating AI into larger, multi-institutional studies is essential to advance the standardization of ICG fluorescence intensity.

In addition, the utility of ICG-guided LN dissection during neoadjuvant chemotherapy (NAC) remains clinically contentious. As previously mentioned, ICG-guided laparoscopic radical gastrectomy and D2 LN dissection significantly increase the median number of LNs recovered, but the effectiveness of ICG in identifying LNs is limited in patients who have undergone neoadjuvant therapy (43.5 vs 37.0, P = 0.312)[53]. Similarly, Huang et al[54] found that patients with significant tumor or LN regression showed no improvement in LN yield or dissection compliance vs non-ICG group, but in patients with no shrinkage of tumor or LNs, the number of LN dissected in the ICG group increased significantly. Lizarralde Capelastegui et al[55] also reported no significant difference in nodal yield between the ICG and non-ICG groups following NAC, a finding that suggests NAC can compromise the efficacy of ICG fluorescence imaging. NAC induces tumor cell apoptosis and necrosis, which stimulates collagen deposition and fibrosis. The resultant dense fibrous tissue compresses surrounding lymphatic vessels, causing luminal stenosis or obstruction that impairs lymphatic drainage and ICG-based fluorescence mapping. Therefore, developing ICG derivatives with superior tissue penetration or combining ICG with complementary tracer techniques can enhance the comprehensive diagnosis of lymphatic vessel obstruction.

Improvement measure

Double tracer: The application of dual tracers has been shown to enhance the accuracy of LN detection. Park et al[56] evaluated the feasibility of simultaneous ICG and 99m-Tc-antimony-sulfur colloid injections for GC and found that the combination of ICG and 99m-Tc-antimony-sulfur colloid resulted in more SLNs being removed than with ICG or 99m-Tc-tin injections alone. Concurrently, the sensitivity and specificity of LN dissection increased to 100%. For GC SLN mapping, dual-tracer laparoscopic pelvic dissection demonstrates superior detection accuracy and sensitivity. However, meta-analysis of SLN biopsy in GC also showed that, compared with the high cost and potential biological hazards of using radioactive materials in the dual-tracer method (radiocolloid tracer + blue dye /ICG), ICG is currently the preferred choice for identifying SLNs in surgery[57]. Therefore, further studies are needed to assess its risk-benefit ratio or to identify a more suitable tracer to facilitate ICG imaging.

Modified ICG: The hydrodynamic diameter can be increased from a minimum of 1 nm ICG to 20 nm to 80 nm ICG-nanocoll by the adsorption of ICG by nanocolloids[58]. Evidence indicates that macromolecular lymphatic tracers with larger hydrodynamic diameters exhibit enhanced SLN tracer retention[59]. Molecules with a hydrodynamic diameter of < 10 nm (ICG) are likely to travel beyond the SLN, while larger molecules with a hydrodynamic diameter of < 100 nm (ICG-nanocoll) are retained in SLN. This size-dependent retention mechanism significantly improves the clinical utility and detection accuracy of SLN mapping in GC via ICG-NIR fluorescence imaging.

In addition, studies have enhanced the capacity of ICG to delineate tumor boundaries during resection and facilitate LN dissection. Shoji et al[60] modified the intraoperative SLN biopsy technique in a small prospective study. During surgery, ICG is injected around the primary tumor to identify SLNs, followed by one-step nucleic acid amplification assay of the resected nodes to rapidly detect metastasis via cytokeratin 19 expression. This approach achieved 85% SLN detection rate with 0% false-negative rate, confirming that the intraoperative diagnosis of LN metastasis using ICG detection of SLN and one-step nucleic acid amplification detection was accurate and feasible. Namikawa et al[61] developed resin-coupled fluorescent ICG endoscopic marker clips to mark the edges. The endoscopic clip equipped with resin-conjugated fluorescent ICG was placed before surgery. The fluorescence signal from ICG in the clip resin can be detected from the outer layer of the serosal surface of the gastrointestinal tract, which helps to determine the resection margin in gastrointestinal cancer.

CONCLUSION

ICG fluorescence imaging has become an integral and transformative tool in modern GC surgery. By significantly improving LN harvest, enabling precise tumor localization, and enhancing visualization of resection margins, it contributes substantially to both the quality of oncologic resection and the accuracy of postoperative staging. However, challenges such as false-negative outcomes and the lack of standardized protocols remain.

ICG is a safe and effective multi-purpose tool, but it requires standardized solutions and cross-disciplinary technical integration. Combining ICG with artificial intelligence and computer vision algorithms holds great potential for real-time, intraoperative decision support, such as predicting LN status and automatically defining optimal resection boundaries. The synergy between ICG fluorescence and robotic surgical systems promises to enhance precision and reproducibility. Furthermore, the development of molecularly targeted fluorescent probes that bind specifically to tumour biomarkers represents a pivotal frontier, aiming to transcend the limitations of current non-specific imaging. Parallel efforts in developing quantitative fluorescence imaging systems will be crucial for removing subjective assessment and establishing an objective framework for signal interpretation.

The future trajectory of ICG imaging lies in technological integration and innovation. In conclusion, through continued refinement, standardization, and its integration with next-generation surgical technologies, ICG fluorescence imaging is poised to solidify its role as an indispensable modality, paving the way toward a new standard of precision in GC surgery. Future efforts must focus on establishing universally accepted guidelines through larger, multi-centre prospective studies.